Desflurane and Surgery Exposure During Pregnancy Decrease Synaptic Integrity and Induce Functional Deficits in Juvenile Offspring Mice

Zou, Sheng; Wei, Zheng Zachory; Yue, Yun; Jiang, Michael Qize; Wu, Anshi

doi:10.1007/s11064-019-02932-z

Cited by 17 publications

(10 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We were neither able to detect any neurocognitive impact. Our results are therefore in line with previous findings showing that maternal surgery during pregnancy does not result in major differences compared to anesthesia without surgery [25], or only in slightly impaired neurological outcome [23, 24, 27]. As the high IUFD is probably the consequence of the susceptibility of fetuses in a small animal model, the results should be confirmed in a large animal model.…”

Section: Discussionsupporting

confidence: 92%

“…The underlying mechanisms for impairment of neurodevelopment after exposure to anesthesia during early childhood or pregnancy remain still unknown. One mechanism that has been suggested is (neuro-) inflammation [24, 70-72]. In our study, we could not document signs of increased maternal inflammation.…”

Section: Resultscontrasting

confidence: 81%

“…The cytokines IL-6 and IL-10 and leukocyte counts were unchanged, and these have been earlier used in rabbits as a measure of inflammation [73, 74]. IL-6 has been previously shown to be involved in the pathways of neuroinflammation, resulting in impaired fetal brain development [24, 70, 71]. Also, the density of microglial cells (marker of neuroinflammation) did not differ.…”

Section: Resultsmentioning

confidence: 99%

“…There is much less evidence of the effects of surgery on fetal brain development. Maternal surgery during pregnancy in rodent models has been reported to impair fetal neurobehavioral outcome [23, 24], but rabbit and guinea pig models did not show (long-term) neurological impairments after laparotomy or carbon dioxide pneumoperitoneum [25, 26]. In neonatal rat models, it has been demonstrated that pain increases neuroapoptosis [27], but the opposite effect has also been reported, suggesting a potentially neuroprotective effect [28].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effects of Maternal Abdominal Surgery on Fetal Brain Development in the Rabbit Model

Bleeser¹,

Veeken²,

Devroe³

et al. 2021

Fetal Diagn Ther

View full text Add to dashboard Cite

Introduction: Anesthesia during pregnancy can impair fetal neurodevelopment, but effects of surgery remain unknown. The aim is to investigate effects of abdominal surgery on fetal brain development. Hypothesis is that surgery impairs outcome. Methods: Pregnant rabbits were randomized at 28 days of gestation to 2 h of general anesthesia (sevoflurane group, n = 6) or to anesthesia plus laparoscopic appendectomy (surgery group, n = 13). On postnatal day 1, neurobehavior of pups was assessed and brains harvested. Primary outcome was neuron density in the frontal cortex, and secondary outcomes included neurobehavioral assessment and other histological parameters. Results: Fetal survival was lower in the surgery group: 54 versus 100% litters alive at birth (p = 0.0442). In alive litters, pup survival until harvesting was 50 versus 69% (p = 0.0352). No differences were observed for primary outcome (p = 0.5114) for surviving pups. Neuron densities were significantly lower in the surgery group in the caudate nucleus (p = 0.0180), but not different in other regions. No differences were observed for secondary outcomes. Conclusions did not change after adjustment for mortality. Conclusion: Abdominal surgery in pregnant rabbits at a gestational age corresponding to the end of human second trimester results in limited neurohistological changes but not in neurobehavioral impairments. High intrauterine mortality limits translation to clinical scenario, where fetal mortality is close to zero.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Resultscontrasting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Maternal Abdominal Surgery on Fetal Brain Development in the Rabbit Model

Bleeser¹,

Veeken²,

Devroe³

et al. 2021

Fetal Diagn Ther

View full text Add to dashboard Cite

show abstract

“…For example, McClaine et al administered anesthetics at an approximately clinical dose to sheep approximately 122 days into pregnancy and found no neurotoxicity through histological evaluation [ 8 ]. However, a new study in 2020 reported that desflurane anesthesia during pregnancy might harm the learning and memory functions of juvenile offspring; mice displayed increased sensitivity to fear conditioning if their mothers were administered 10% desflurane for 3 h while gestating them [ 9 ]. Another study showed that the inhalational anesthetic sevoflurane could act on the fetus through the placenta and that high-dose, long-term exposure posed the highest degree of neurotoxicity risk to fetal and juvenile mice [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of sevoflurane exposure during different stages of pregnancy on the brain development of rat offspring

Cui

et al. 2021

J Anesth

View full text Add to dashboard Cite

Objective This study explored the effects of sevoflurane exposure during different stages of pregnancy on the brain development of offspring. Methods Thirty-six pregnant SD rats were randomly divided into 4 groups: control, sevoflurane exposure in early (S1) pregnancy, sevoflurane exposure in middle (S2) pregnancy, and sevoflurane exposure in late (S3) pregnancy. After natural birth, the learning and memory capacity of offspring rats was analyzed using the Morris water maze experiment. The hippocampi of offspring rats were collected. The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus were measured by ELISA. Additionally, the Nissl bodies in the hippocampus were analyzed using Nissl staining. Immunohistochemistry was used to examine the expression of BDNF and CPEB2 in the hippocampus of offspring. Proteins related to the NR4A1/NF-κB pathway were analyzed using western blotting. Results The memory and learning capacity of offspring rats was significantly reduced in the S1 and S2 groups compared to the control group (p < 0.05), while there was no obvious difference between the control and S3 groups (p > 0.05). The level of IL-1β was significantly increased (p < 0.05) in the S1 group compared with the control group. Sevoflurane anesthesia received in early and middle pregnancy could significantly affect the formation of Nissl bodies in the hippocampi of offspring rats. In addition, the expression of BDNF and CPEB2 in the hippocampi of offspring rats was greatly decreased in the S1 group compared with the control group (p < 0.05). The expression of NR4A1 in the hippocampi of rat offspring was significantly decreased in the S1 and S2 groups compared with the control group (p < 0.05). The expression of proteins related to the NF-κB pathway was increased in the S1 group compared to the control group (p < 0.05). Conclusions The neurotoxic effect of maternal sevoflurane anesthesia on the brain development of offspring is higher when the exposure occurs in early pregnancy than in late pregnancy, and its mechanism might involve the NR4A1/NF-κB pathway to increase the secretion of inflammatory cytokines.

show abstract

Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane‐exposed offspring mice

Zhang,

Wei,

Jing

et al. 2024

Brain and Behavior

View full text Add to dashboard Cite

IntroductionPregnant women may need to undergo non‐obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane‐induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO‐induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO.MethodsPregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00–18:00 h) during GD15–21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti‐inflammatory markers and synaptic function‐related proteins were assessed using molecular biology methods.ResultsThe results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐alpha and a reduction in the hippocampal levels of IL‐10, synaptophysin, post‐synaptic density‐95, growth‐associated protein‐43, and brain‐derived neurotrophic factor.ConclusionOur findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.

show abstract

Desflurane and Surgery Exposure During Pregnancy Decrease Synaptic Integrity and Induce Functional Deficits in Juvenile Offspring Mice

Cited by 17 publications

References 45 publications

Effects of Maternal Abdominal Surgery on Fetal Brain Development in the Rabbit Model

Effects of Maternal Abdominal Surgery on Fetal Brain Development in the Rabbit Model

Effects of sevoflurane exposure during different stages of pregnancy on the brain development of rat offspring

Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane‐exposed offspring mice

Contact Info

Product

Resources

About